Adverse cutaneous photosensitivity reactions following exposure to environmental chemicals and light have been reported with increasing frequency during recent years. The broad objective of our research is to define more precisely the underlying mechanisms of these adverse photoresponses. Our approach is to work in the interface between isolated test tube photochemical studies and the physiologic, but highly complex photobiologic responses in the whole organism. Specifically, this year our goals include: 1) To determine whether or not the formation of photoadducts between chlorpromazine and DNA is related to cellular phototoxicity of chlorpromazine. b) To determine the mechanism of DNA chain scission induced by photoactivated chlorpromazine. c) To correlate the reactivity toward cell lysis of the protriptyline photoproducts with their chemical structures. d) To characterize in detail the photochemical and immunological processes which initiate the cutaneous photosensitivity responses to musk ambrette and to 6-methylcoumarin.